Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells

Alexandra Traister, Igal Breitman, Ella Bar-Lev, Isabel Zvibel, Avikam Harel, Zamir Halpern, Ran Oren

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Nicotinamide has been shown to inhibit proliferation and induce apoptosis in a variety of cells. Moreover, nicotinamide treatment attenuates collagen accumulation and fibrogenesis in the bleomycin model of lung fibrosis. We hypothesized that nicotinamide may be useful as an antifibrotic agent in liver fibrosis and we investigated the in vitro effect of nicotinamide on hepatic stellate cells proliferation, apoptosis and collagen I expression. Material and methods. Transforming growth factor β1 (TGF-β1) was used for activation of the rat HSC-T6 cell line. Apoptosis was determined by fluorescence activated cell sorter (FACS) analysis after propidium iodide staining and by immunohistochemistry showing presence of the active form of caspase 3. Expression of activation marker α-smooth muscle actin (α-SMA), apoptotic and cell cycle markers cyclin D1, P53 and caspase 3 was determined by Western blotting. Collagen I expression was assessed by Northern blotting. Results. Nicotinamide inhibits hepatic stellate cell proliferation and induces apoptosis with caspase-3 activation. There is no effect of nicotinamide on the levels of cell cycle stimulator cyclin D1. Expression of p53 is induced in the presence of nicotinamide. Nicotinamide reduces activation marker α-SMA and decreases both basal and TGFβ-induced collagen I expression. Moreover, in TGFβ-activated cells, nicotinamide reduces expression of pro-inflammatory and profibrotic cytokines TGFβ2, IL-1β, TNFα and macrophage chemotactic protein-1. Conclusions. The in vitro effect of nicotinamide on activation and proliferation of hepatic stellate cells suggests that nicotinamide may have a potential beneficial role in attenuation of liver fibrogenesis.

Original languageEnglish
Pages (from-to)1226-1234
Number of pages9
JournalScandinavian Journal of Gastroenterology
Volume40
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Cytokines
  • Hepatic stellate cells
  • Nicotinamide

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